a. Field of Invention
This invention relates to the cyclic dodecapeptide, triglycyl-lysine vasopressin or also called triglycyl-vasopressin, of the formula ##STR2## More particularly this invention relates to an improved process for preparing triglycyl-lysine vasopressin and to intermediates used for the process.
B. Prior Art
The name "vasopressin" has been proposed for the factor found in pituitary extracts which controls the water balance as well as exhibiting other biological effects (see review by E. Schroder and K. Lubke in "The Peptides" Vol. 11, pp 336-358, Academic Press, New York and London, 1966).
A number of analogs of lysine vasopressin were prepared by E. Kasafirek et al, Coll. Czech. Chem. Commun., 31 4581(1966), most notably triglycyl-lysine vasopressin. Results from clinical trials by J. H. Cort et al, Europ. J. Clin. Invest., 5, 165-175(1975), show that this peptide has a prolonged effect on uterine contractions, thus useful for initiating abortive menstruation and in addition the peptide inhibits bleeding from both the gut and uterus.
The report relating to the synthesis of triglycyl-lysine vasopressin by Kasafirek et al, supra, does not give the experimental details for the preparation of the cyclic dodecapeptide. However, by analogy with the process used for the preparation of the other vasopressin analog in the same report, the over-all yield of the process for the vasopressin analog apparently is very low. In addition, it should be noted that the synthesis utilizes very stable protecting groups which require severe conditions for their removal.
In keeping with the need for a practical synthesis of the cyclic dodecapeptide, triglycyl-lysine vasopressin, the present invention discloses a new practical process for the large scale preparation of the cyclic dodecapeptide. Furthermore the present process has additional advantages in that it starts from readily available materials, avoids noxious reagents, is executed facilely, utilizes easily removable protecting groups and provides a pure product in high yield with a high degree of physiological potency.